ClinVar Miner

Submissions for variant NM_000170.2(GLDC):c.1926+5G>A (rs1554644678)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000534696 SCV000798388 uncertain significance Non-ketotic hyperglycinemia 2018-03-08 criteria provided, single submitter clinical testing
Invitae RCV000534696 SCV000636369 likely pathogenic Non-ketotic hyperglycinemia 2017-08-10 criteria provided, single submitter clinical testing This sequence change falls in intron 16 of the GLDC gene. It does not directly change the encoded amino acid sequence of the GLDC protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in two individuals affected with glycine encephalopathy (PMID: 27362913, Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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